title: Repetitive myocardial ischemia promotes coronary growth in the adult mammalian heart.
abstract: BACKGROUND
  Coronary artery disease and ischemic cardiomyopathy represent the leading cause of heart failure and continue to grow at exponential rates. Despite widespread availability of coronary bypass surgery and percutaneous coronary intervention, subsequent ischemic events and progression to heart failure continue to be common occurrences. Previous studies have shown that a subgroup of patients develop collateral blood vessels that serve to connect patent and occluded arteries and restore perfusion to ischemic territories. The presence of coronary collaterals has been correlated with improved clinical outcomes; however, the molecular mechanisms governing this process remain largely unknown.
  
  
  RESULTS
  To date, no mouse models of coronary arterial growth have been described. Using a closed-chest model of myocardial ischemia, we have demonstrated that brief episodes of repetitive ischemia are sufficient to promote the growth of both large coronary arteries and the microvasculature. Induction of large coronary artery and microvascular growth resulted in improvements in myocardial perfusion after prolonged ischemia and protected from subsequent myocardial infarction. We further show that repetitive ischemia did not lead to increased expression of classic proangiogenic factors but instead resulted in activation of the innate immune system and recruitment of macrophages to growing blood vessels.
  
  
  CONCLUSIONS
  These studies describe a novel model of coronary angiogenesis and implicate the cardiac macrophage as a potential mediator of ischemia-driven coronary growth.
authors.affiliation: Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Kory J
authors.initials: KJ
authors.lastname: Lavine
authors.forename: Attila
authors.initials: A
authors.lastname: Kovacs
authors.forename: Carla
authors.initials: C
authors.lastname: Weinheimer
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000367:Age Factors; D000818:Animals; D003331:Coronary Vessels / Q000254:growth & development*; D004195:Disease Models, Animal; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000254:growth & development*; D017202:Myocardial Ischemia; D018919:Neovascularization, Physiologic
keywords: collateral; coronary; coronary angiogenesis; macrophage; repetitive ischemia